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Characterizing the tumor microenvironment in rare renal cancer histological types

The tumor microenvironment (TME), including immune cells, cancer‐associated fibroblasts, endothelial cells, adjacent normal cells, and others, plays a crucial role in influencing tumor behavior and progression. Here, we characterized the TME in 83 primary renal tumors and matched metastatic or recur...

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Autores principales: Synnott, Naoise C, Poeta, Maria Luana, Costantini, Manuela, Pfeiffer, Ruth M, Li, Mengying, Golubeva, Yelena, Lawrence, Scott, Mutreja, Karun, Amoreo, Carla, Dabrowska, Malgorzata, Simone, Giuseppe, Pescarmona, Edoardo, Lenz, Petra, Olanich, Mary, Duggan, Maire, Abubakar, Mustapha, Fazio, Vito Michele, Gallucci, Michele, Sentinelli, Steno, Landi, Maria Teresa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8682943/
https://www.ncbi.nlm.nih.gov/pubmed/34618413
http://dx.doi.org/10.1002/cjp2.241
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author Synnott, Naoise C
Poeta, Maria Luana
Costantini, Manuela
Pfeiffer, Ruth M
Li, Mengying
Golubeva, Yelena
Lawrence, Scott
Mutreja, Karun
Amoreo, Carla
Dabrowska, Malgorzata
Simone, Giuseppe
Pescarmona, Edoardo
Lenz, Petra
Olanich, Mary
Duggan, Maire
Abubakar, Mustapha
Fazio, Vito Michele
Gallucci, Michele
Sentinelli, Steno
Landi, Maria Teresa
author_facet Synnott, Naoise C
Poeta, Maria Luana
Costantini, Manuela
Pfeiffer, Ruth M
Li, Mengying
Golubeva, Yelena
Lawrence, Scott
Mutreja, Karun
Amoreo, Carla
Dabrowska, Malgorzata
Simone, Giuseppe
Pescarmona, Edoardo
Lenz, Petra
Olanich, Mary
Duggan, Maire
Abubakar, Mustapha
Fazio, Vito Michele
Gallucci, Michele
Sentinelli, Steno
Landi, Maria Teresa
author_sort Synnott, Naoise C
collection PubMed
description The tumor microenvironment (TME), including immune cells, cancer‐associated fibroblasts, endothelial cells, adjacent normal cells, and others, plays a crucial role in influencing tumor behavior and progression. Here, we characterized the TME in 83 primary renal tumors and matched metastatic or recurrence tissue samples (n = 15) from papillary renal cell carcinoma (pRCC) types 1 (n = 20) and 2 (n = 49), collecting duct carcinomas (CDC; n = 14), and high‐grade urothelial carcinomas (HGUC; n = 5). We investigated 10 different markers of immune infiltration, vasculature, cell proliferation, and epithelial‐to‐mesenchymal transition by using machine learning image analysis in conjunction with immunohistochemistry. Marker expression was compared by Mann–Whitney and Kruskal–Wallis tests and correlations across markers using Spearman's rank correlation coefficient. Multivariable Poisson regression analysis was used to compare marker expression between histological types, while accounting for variation in tissue size. Several immune markers showed different rates of expression across histological types of renal carcinoma. Using pRCC1 as reference, the incidence rate ratio (IRR) of CD3+ T cells (IRR [95% confidence interval, CI] = 2.48 [1.53–4.01]) and CD20+ B cells (IRR [95% CI] = 4.38 [1.22–5.58]) was statistically significantly higher in CDC. In contrast, CD68+ macrophages predominated in pRCC1 (IRR [95% CI] = 2.35 [1.42–3.9]). Spatial analysis revealed CD3+ T‐cell and CD20+ B‐cell expressions in CDC to be higher at the proximal (p < 0.0001) and distal (p < 0.0001) tumor periphery than within the central tumor core. In contrast, expression of CD68+ macrophages in pRCC2 was higher in the tumor center compared to the proximal (p = 0.0451) tumor periphery and pRCC1 showed a distance‐dependent reduction, from the central tumor, in CD68+ macrophages with the lowest expression of CD68 marker at the distal tumor periphery (p = 0.004). This study provides novel insights into the TME of rare kidney cancer types, which are often understudied. Our findings of differences in marker expression and localization by histological subtype could have implications for tumor progression and response to immunotherapies or other targeted therapies.
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spelling pubmed-86829432021-12-30 Characterizing the tumor microenvironment in rare renal cancer histological types Synnott, Naoise C Poeta, Maria Luana Costantini, Manuela Pfeiffer, Ruth M Li, Mengying Golubeva, Yelena Lawrence, Scott Mutreja, Karun Amoreo, Carla Dabrowska, Malgorzata Simone, Giuseppe Pescarmona, Edoardo Lenz, Petra Olanich, Mary Duggan, Maire Abubakar, Mustapha Fazio, Vito Michele Gallucci, Michele Sentinelli, Steno Landi, Maria Teresa J Pathol Clin Res Original Articles The tumor microenvironment (TME), including immune cells, cancer‐associated fibroblasts, endothelial cells, adjacent normal cells, and others, plays a crucial role in influencing tumor behavior and progression. Here, we characterized the TME in 83 primary renal tumors and matched metastatic or recurrence tissue samples (n = 15) from papillary renal cell carcinoma (pRCC) types 1 (n = 20) and 2 (n = 49), collecting duct carcinomas (CDC; n = 14), and high‐grade urothelial carcinomas (HGUC; n = 5). We investigated 10 different markers of immune infiltration, vasculature, cell proliferation, and epithelial‐to‐mesenchymal transition by using machine learning image analysis in conjunction with immunohistochemistry. Marker expression was compared by Mann–Whitney and Kruskal–Wallis tests and correlations across markers using Spearman's rank correlation coefficient. Multivariable Poisson regression analysis was used to compare marker expression between histological types, while accounting for variation in tissue size. Several immune markers showed different rates of expression across histological types of renal carcinoma. Using pRCC1 as reference, the incidence rate ratio (IRR) of CD3+ T cells (IRR [95% confidence interval, CI] = 2.48 [1.53–4.01]) and CD20+ B cells (IRR [95% CI] = 4.38 [1.22–5.58]) was statistically significantly higher in CDC. In contrast, CD68+ macrophages predominated in pRCC1 (IRR [95% CI] = 2.35 [1.42–3.9]). Spatial analysis revealed CD3+ T‐cell and CD20+ B‐cell expressions in CDC to be higher at the proximal (p < 0.0001) and distal (p < 0.0001) tumor periphery than within the central tumor core. In contrast, expression of CD68+ macrophages in pRCC2 was higher in the tumor center compared to the proximal (p = 0.0451) tumor periphery and pRCC1 showed a distance‐dependent reduction, from the central tumor, in CD68+ macrophages with the lowest expression of CD68 marker at the distal tumor periphery (p = 0.004). This study provides novel insights into the TME of rare kidney cancer types, which are often understudied. Our findings of differences in marker expression and localization by histological subtype could have implications for tumor progression and response to immunotherapies or other targeted therapies. John Wiley & Sons, Inc. 2021-10-07 /pmc/articles/PMC8682943/ /pubmed/34618413 http://dx.doi.org/10.1002/cjp2.241 Text en © 2021 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd. This article has been contributed to by US Government employees and their work is in the public domain in the USA. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Synnott, Naoise C
Poeta, Maria Luana
Costantini, Manuela
Pfeiffer, Ruth M
Li, Mengying
Golubeva, Yelena
Lawrence, Scott
Mutreja, Karun
Amoreo, Carla
Dabrowska, Malgorzata
Simone, Giuseppe
Pescarmona, Edoardo
Lenz, Petra
Olanich, Mary
Duggan, Maire
Abubakar, Mustapha
Fazio, Vito Michele
Gallucci, Michele
Sentinelli, Steno
Landi, Maria Teresa
Characterizing the tumor microenvironment in rare renal cancer histological types
title Characterizing the tumor microenvironment in rare renal cancer histological types
title_full Characterizing the tumor microenvironment in rare renal cancer histological types
title_fullStr Characterizing the tumor microenvironment in rare renal cancer histological types
title_full_unstemmed Characterizing the tumor microenvironment in rare renal cancer histological types
title_short Characterizing the tumor microenvironment in rare renal cancer histological types
title_sort characterizing the tumor microenvironment in rare renal cancer histological types
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8682943/
https://www.ncbi.nlm.nih.gov/pubmed/34618413
http://dx.doi.org/10.1002/cjp2.241
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